ABSTRACT
Objective To probe the different expression of psychomotor in different model of pretreatment and the influence of pretreatment context on the expression of psychomotor.And to compare dopaminergic and non-dopaminergic neuron activity in midbrain after different pretreatment.Methods Rats were pretreated by escalated high-dose morphine( HD group) ,fixed low-dose morphine( LD group) and saline as control(S group).After withdrawal, rats were challenged by morphine in non-drug used environment.Locomotor behavior and stereotypy behavior were monitored as the index of compulsive drug-seeking motivation.By double labeling immunohistochemistry of tyrosine hydroxylase (TH) and Fos protein, the plasticity of neuronal activity in ventral tegmental area and substantia nigra of rats response to morphine challenge were disclose after pretreated with morphine or saline.Results After 10 mg/kg morphine challenge in non-drug used environment,the locomotor behavior and the stereotypy behavior of HD group were both significant higher than that of S group ( Locomotor behavior and Stereotypy behavior,HD group: 26907 ± 2003 and 129.6 ± 6.5; S group: 14962 ± 1888 and 89.9 ± 10.9, all P ＜ 0.01 ).The results of immunohistochemistry showed that Fos protein expressed in the SNr and in lateral SNr was significantly higher in the HD group compared to S groups ( Fos expression in SNr and lateral SNr,HD group: 29.14 ±5.27 and 9.83 ± 2.84; S group: 17.29 ± 1.51 and 2.06 ±0.45; all P＜0.05 ).Conclusion The sensitization behavior expression of the rat pretreated by escalated high-dose morphine is not modulated by drug using enviroment compared with fixed low-dose morphine pretreatment.The neuroplasticity of SNr,especially lateral SNr might be one of the mechanisms underlying the uncontroled sensitization behavior expression.
ABSTRACT
OBJECTIVE: It was hypothesized that dopamine agonist administration and subthalamic nucleus (STN) lesion in the rat might have a synergistic effect on the neuronal activities of substantia nigra pars reticulata (SNpr) as observed in patients with Parkinson's disease. The effects of SKF38393 (a D1 receptor agonist) and Quinpirole (a D2 receptor agonist) were compared in parkinsonian rat models with 6- hydroxydopamine (6-OHDA) after STN lesion. METHODS: SKF38393 and Quinpirole were consecutively injected intrastriatally. SNpr was microrecorded to ascertain the activity of the basal ganglia output structure. The effect of SKF38393 or Quinpirole injection on the firing rate and firing patterns of SNpr was investigated in medial forebrain bundle (MFB) lesioned rats and in MFB+STN lesioned rats. RESULTS: The administration of SKF38393 decreased SNpr neuronal firing rates and the percentage of burst neurons in the MFB lesioned rats, but did not alter them in MFB+STN lesioned rats. The administration of Quinpirole significantly decreased the spontaneous firing rate in the MFB lesioned rats. However, after an additional STN lesion, it increased the percentage of burst neurons. CONCLUSION: This study demonstrated that dopamine agonists and STN lesion decreased the hyperactive firing rate and the percentage of burst neurons of SNpr neurons in 6-OHDA lesioned rats, respectively. Quinpirole with STN lesion increased a percentage of burst neurons. To clear the exact interactive mechanism of D1 and D2 agonist and the corresponding location, it should be followed a study using a nonselective dopamine agonist and D1, D2 selective antagonist.